Quantitating the Percutaneous Absorption of Mechanistically-Defined Chemical Mixtures

摘要

The focus of this research was to assess the dermal absorption and skin toxicity of topically applied jet fuels Jet A, JP-8, JP-8(100) using pigs, in vitro porcine skin and inert membrane models as well as human keratinocyte cell cultures. Our working hypothesis was that jet fuel dermal toxicity was secondary to its hydrocarbon components with differences between fuel types due to additive-modulation of hydrocarbon deposition. Consistent with previous JP-8 additive studies, individual JP-8(lOO) additives modulated hydrocarbon disposition. Combinations of multiple additives were not predictable from simpler mixtures. An in vivo porcine skin dose escalation study demonstrated dose-related dermal absorption of aromatics, but saturation of aliphatic components. Previous exposure to JP-8 constituents resulted in skin depot formation. Cell culture studies demonstrated divergent relations between structure and resulting cytotoxicity and irritation (11-8 release). Across S aliphatic and 6 aromatic hydrocarbons studied in vivo, tridecane, tetradecane and pentadecane produced gross and microscopic lesions similar to JP-8, suggesting they may be responsible for JP-8 irritation. Ultrastructural changes were characterized by alterations in the stratum corneum lipid bilayers. Finally, a novel membrane coated fiber technique was developed that was capable of rapidly determining physical chemical properties of all jet fuel hydrocarbon constituents as well as assessina additive and solvent effects on membrane diffusion and partitioning.